Genetic Testing - Wolman Disease ..., (Wolman Disease) - Gen LIPA.

Wolman disease is a rare inherited disorder that affects lipid metabolism (degradation and synthesis of fat and cholesterol) in the body. In affected individuals, harmful amounts of lipids in the spleen, liver, bone marrow, small intestine, adrenal glands, lymph nodes and accumulate. In addition to fatty deposits, calcium deposits are also observed in the adrenal glands.

Children with Wolman disease are healthy at birth, but early signs and symptoms of the disease develop. These may include hepatosplenomegaly, poor weight gain, low muscle tone, and jaundice, vomiting, diarrhea, failure to thrive, anemia, and malabsorption of nutrients from food, so show significant malnutrition and generally do not survive beyond early childhood.

This process is due to mutations in the LIPA gene, located on the long arm of chromosome 10 (10q23.2-q23.3). LIPA gene encoding the lysosomal acid lipase enzyme. This enzyme is found in lysosomes where processing lipids as cholesterol esters and triglycerides that may be used by the body. Mutations in this gene cause a shortage of lysosomal acid lipase and triglyceride accumulation, cholesterol esters and other fats within cells and tissues of affected individuals. This accumulation and malnutrition caused by the body's inability to properly use lipids lead to signs and symptoms of the disease. In general, a lower activity of lysosomal acid lipase causes a more severe illness.

We found more than 10 mutations in the gene that cause the disorder LIPA. The most common LIPA mutation that causes the disease replaces a guanine by adenine near exon 8 (IVS8-1G> A). This mutation alters the instructions synthesizing enzyme gene, which leads to suppression of 24 amino acids. People with a mutation IVS8-1G> in both copies of the gene in each cell LIPA have only 5 percent of the normal amount of lysosomal lipase activity.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with Wolman disease by the complete PCR amplification of the exons of the gene LIPA respectively, and subsequent sequencing.